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Other methylxanthines produced a similar, but less marked, effect. The elevation of ACE seemed to require de novo protein synthesis since it was reduced by 0.1 \u03bc\/ml cycloheximide. Elevation of cellular cAMP was detected at 30 min after introduction of IBMX, then rapidly returned to control levels at 1 hour, while elevation in cellular ACE at 24 hr required contact with IBMX for at least 2 hr. Hence, the transient elevation in cAMP is unlikely to be the cause of the elevation of ACE. Phorbol ester and synthetic diacyl glycerol OAG, activtors of protein kinase C, did not elevate ACE. Indomethacin, at a concentration known to inhibit cycloxygenase activity, had no effect on the elevation of ACE. The elevation of ACE by IBMX was not affected by the calcium channel blocker verapamil or the calcium chelator EGTA. In contrast, the effect of IBMX was totally abolished by the calmodulin inhibitors trifluoperazine and calmidazolium. The data show that IBMX elevates endothelial cell ACE and suggest that the elevation is mediated by a calcium\u2010calmodulin complex. The studies demonstrate a novel effect of methylxanthines on endothelial cells in culture.<\/jats:p>","DOI":"10.1002\/jcp.1041370122","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T10:55:56Z","timestamp":1109415356000},"page":"179-184","source":"Crossref","is-referenced-by-count":15,"title":["Elevation of angiotensin converting enzyme by 3\u2010isobutyl\u20101\u2010methylxanthine in cultured endothelial cells: A possible role for calmodulin"],"prefix":"10.1002","volume":"137","author":[{"given":"Yamuna","family":"Dasarathy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry L.","family":"Fanburg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.4049\/jimmunol.140.1.208","article-title":"Potentiation of lymphokine\u2010activated killer cell differentiation and lymphocyte proliferation by stimulation of protein kinase C or inhibition of adenylate cyclase","volume":"140","author":"Beckner S. 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